Investigation of comprehensive etiology of microcephaly with pontocerebellar hypoplasia (MICPCH)

2014 Fiscal Year Final Research Report

• Project/Area Number: 25830135
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: HAYASHI Shin 東京医科歯科大学, 硬組織疾患ゲノムセンター, 特任講師 (50596244)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: CASK / MICPCH / 小頭症 / 小脳脳幹部低形成 / 疾患関連遺伝子 / 疾患コホート / 次世代シークエンサー

Outline of Final Research Achievements

In order to investigate an etiology of microcephaly with pontocerebellar hypoplasia (MICPCH) we analyzed mutation of CASK, which is a major causative gene of MICPCH, and investigated novel causative gene using next-generation sequencer for a cohort of 40 patients with typical MICPCH. Besides haploinsufficiency of CASK in 28 patients, we identified mutation of ITPR1 as a known causative gene, and RELN, Genes A and B as a candidate causative gene. Moreover we identified Gene B was corresponding to neural differentiation and Gene A potentially activated an expression of Gene B through a suppression of expression of Gene A and/or Gene B on cell-line from neuroblastoma, suggesting that haploinsufficiency of both genes could cause MICPCH.

Free Research Field

遺伝学